Several highly bridged peptides are known in the literature, for example conopeptides isolated from cone snails (for a review see e.g. Terlau & Olivera, Physiol. Rev. 2004, 84, 41-68) or the so-called lantibiotics (Chatterjee et al., Chem. Rev. 2005, 105, 633-683) from Gram-positive bacteria source. The said peptides have various utilities. The lantibiotic nisin has been used, among other utilities, as a food preservative since many years.
The conopeptides are useful, for example, for the treatment of pain, diabetes, multiple sclerosis and cardiovascular diseases and currently undergo preclinical or clinical development. Examples of conopeptides are α-GI (sequence: ECCNPACGRHYSC*, *amidated, connectivity: 1-3,2-4) and α-GID (sequence: IRγCCSNPACRVNNOHVC, connectivity: 1-3,2-4), wherein O/Hyp is hydroxyproline and the connectivity indicates the position of the cysteine involved in each specific disulphide bonds, for example, first to third and second to fourth as in α-GID:
